Prosthetic devices are artificial devices used to replace or strengthen a particular part of the human body. Various prosthetic devices are available, such as joint replacement prosthesis, stent prosthesis and vascular graft prosthesis. When implanting a prosthesis, such as a stent prosthesis described in greater detail herein, it is desireable that the prosthesis closely assimilate the characteristics of the tissue or bone that the prosthesis is designed to repair or replace. To this end, many attempts have been made to improve biocompatible and mechanical properties of prosthetic devices. Also, it can be desirable to topically medicate the area where the prosthetic has been implanted.
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially compress against the atherosclerotic plaque of the lesion to remodel the vessel wall. The balloon is deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature.
A problem associated with the above procedure includes formation of intimal flaps or torn arterial linings which can collapse and occlude the conduit after develop over several months after the procedure, which may require another angoioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, an expandable intraluminal prosthesis, one example of which includes a stent, is implanted in the lumen to maintain the vascular patency.
Percutaneous endovascular prosthetic stents were conceived in the late 1970's as a way to prevent both acute occlusion and late restenosis after catheter intervention, but initial clinical results of coronary stenting in 1987 were plagued by high (>20%) acute and subacute thrombosis and were restricted to use as “bailout” for threatened or acute vessel closure. In recent years, stent outcomes have improved progressively with better placement techniques and in 1995, an estimated 700,000 stents were implanted world-wide.
Stents are scaffoldings, usually cylindrical or tubular in shape, which function to physically hold open and, if desired, to expand the wall of the passageway. Typically stents are capable of being compressed for insertion through small cavities via small catheters, and expanded to a larger diameter once at the desired location.
To treat the damaged vasculature tissue and assist prevention of thrombosis and restenosis, there is a need for administrating therapeutic substances to the treatment site. For example, anticoagulants, antiplatelets and cytostatic agents are commonly used to prevent thrombosis of the coronary lumen, to inhibit development of restenosis, and to reduce post-angioplasty proliferation of the vascular tissue, respectively. To provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery can be a preferred method of treatment in that smaller total levels of medication are administered at a specific site in comparison to larger overall dosages that are applied systemically. Local delivery produces fewer side effects and achieves more effective results.
One commonly applied technique for the local delivery of a drug is through the use of a polymeric carrier coated onto the surface of a stent by applying to a stent body a solution which includes a specified solvent, a specified polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend. The solvent is allowed to evaporate, leaving on the stent surface a coating of the polymer and the therapeutic substance impregnated in the polymer.
Stents sometimes have to be immersed in a coating solution 12 to 15 times or sprayed 20 times to achieve a satisfactory coating. The immersion method of coating a stent, also called dip-coating, entails submerging the entire stent, or an entire section of the stent, in a coating solution. Similarly, spray-coating requires enveloping the entire stent, or an entire section of the stent, in a large cloud of coating material. Disadvantages of dip-coating and spray-coating methods include the inability to control the exact portions of the stent that come in contact with the coating. Another shortcoming of both dip- and spray-coating is the possibility of forming web-like defects by build-up of excess coating material between the stent struts. Web-like defects are most prevalent in stents having tight patterns, for example coronary stents, such that the distance between the struts is very small.
Each of the methods and devices intended for use just prior to implantation, listed above, deposit the coating material onto any and all surfaces that are exposed to the coating. This may result in depositing coating material on surfaces on which the coating is unwanted or undesirable. Further, the coating may crack or break away when the implantable is removed from the implantation apparatus. An example of this would be a stent deployed on a catheter balloon. As the balloon is inflated and the stent is expanded into position, the coating may crack along the interface between the stent and the balloon. These cracks may lead to a breaking away of a portion of the coating from the stent itself. This, in turn, may affect the medicinal effectiveness of the coating, and negatively affect the entire medical procedure.
Another disadvantage of both dip-coating and spray-coating stems from a low-viscosity requirement for the polymer solution in which the stent is dipped or with which the stent is sprayed. A low viscosity coating solution typically require using a low molecular weight carrier or by using a very low concentration of carrier in the coating solution. Thus, both dip-coating and spray-coating methods have imposed limitations in type and concentration of applied carriers.
Accordingly, it is desirable to provide an improved method of applying a coating to a prosthesis. Specifically, it is desirable to provide a method of applying a polymeric coating to a prosthesis which enables control over the portion of the prosthesis which are coated, reduces the incidence of web-like defects due to excess build-up of polymeric material, broadens the field of both the types and the concentrations of carriers which may be used to coat a prosthesis, and allows a prosthesis to be coated with a polymer and a drug at the same time.
The significance of delivering drug-loaded prostheses may offer savings benefit in time and cost. Studies have been conducted to show the importance of delivering the correct drug dose density on coronary stents to prevent restenosis by application of paclitaxel or rapamycin. Kandazari, David E. et al., Highlights from American Heart Association Annual Scientific Sessions 2001: Nov. 11 to 14, 2001, American Heart Journal 143 (2), 217-228, 2002; Hiatt, Bonnie L. et al., Drug-Eluting Stents for Prevention of Restenosis: In Quest for the Holy Grail, Catheterization and Cardiovascular Interventions 55:409-417, 2002; Kalinowski, M. et al., Paclitaxel Inhibits Proliferation Of Cell Lines Responsible For Metal Stent Obstruction: Possible Topical Application In Malignant Bile Duct Obstructions, Investigational Radiology 37(7):399-404, 2002. Other studies have shown how accuracy of dose related to cytotoxicity of coating drugs. Liebmann, J. E .et al., Cytotoxic Studies Of Paclitaxel (Taxol) In Human Tumor Cell Lines, Br. J. Cancer, 68(6):1104-9, 1993; Adler, L. M. et al., Analysis Of Exposure Times And Dose Escalation Of Paclitaxel In Ovarian Cancer Cell Lines, Cancer, 74(7):1891-8, 1994; Regar, E. et al., Stent Development And Local Drug Delivery, Br. Med. Bulletin, 59:227-48, 2001. See also http://www.tctmd.com/expert-presentations: Farb, A., Comparative Pathology Of Drug Eluting Stents: Insights Into Effectiveness And Toxicity From Animal Lab, CRF Drug-Eluting Stent Symposium 2002; Grube, E., Taxol-Eluting Stent Trials, ISET 2002 Miami Beach, Mar. 19-23, 2002 (The effect of taxol on the edges of the stent and dose response screening); Carter, Andrew J., Sirolimus: Pre-Clinical Studies—Evaluation Of Dosing, Efficacy And Toxicity, TCT September 2001.
Accordingly, the desired features of the invention comprise an apparatus and method for coating a prosthesis which avoid the disadvantages of dip-coating and spray coating methods. In addition, coating the prosthesis can be achieved with such control such that the prosthesis can be coated in the operating room prior to insertion of the prosthesis into the patient, thus avoiding coating portions of the prosthesis or prosthesis handling apparatus, such as a catheter, where such a coating is not desirable.
This is achieved by using contact printing techniques which take advantage of known methods of lithography using self-assembled monolayers. Coating desired portions of the prosthesis can be achieved by stamping the prosthesis with a coating that can form a self-assembled monolayer. The surface of the applicator is coated or saturated with the coating and the applicator is placed in contact with the surface of the prosthesis to be coated to transfer the coating from the applicator to the prosthesis surface.
To form a pattern on a arcuate or curved prosthesis surface, including but not limited to a cylindrical surface, the prosthesis can be rolled over a planar applicator or the prosthesis can be rolled over a curved